J Cancer 2022; 13(8):2656-2661. doi:10.7150/jca.71494 This issue

Research Paper

Effect of Atezolizumab plus Bevacizumab in Patients with Hepatocellular Carcinoma Harboring CTNNB1 Mutation in Early Clinical Experience

Keita Ogawa1,*, Hiroaki Kanzaki1,*, Tetsuhiro Chiba1,✉, Junjie Ao1, Na Qiang1, Yaojia Ma1, Jiaqi Zhang1, Sae Yumita1, Takamasa Ishino1, Hidemi Unozawa1, Motoyasu Kan1, Terunao Iwanaga1, Miyuki Nakagawa1, Kisako Fujiwara1, Naoto Fujita1, Takafumi Sakuma1, Keisuke Koroki1, Yuko Kusakabe1, Kazufumi Kobayashi1, Naoya Kanogawa1, Soichiro Kiyono1, Masato Nakamura1, Takayuki Kondo1, Tomoko Saito1, Ryo Nakagawa1, Sadahisa Ogasawara1, Eiichiro Suzuki1, Shingo Nakamoto1, Ryosuke Muroyama2, Tatsuo Kanda3, Hitoshi Maruyama4, Naoya Mimura5, Jun Kato1, Shinichiro Motohashi6, Naoya Kato1

1. Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan
2. Department of Molecular Virology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan
3. Department of Gastroenterology and Hepatology, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo 173-8610, Japan
4. Department of Gastroenterology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
5. Department of Transfusion Medicine and Cell Therapy, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan
6. Department of Medical Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan
*These authors contributed equally to this work.

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Citation:
Ogawa K, Kanzaki H, Chiba T, Ao J, Qiang N, Ma Y, Zhang J, Yumita S, Ishino T, Unozawa H, Kan M, Iwanaga T, Nakagawa M, Fujiwara K, Fujita N, Sakuma T, Koroki K, Kusakabe Y, Kobayashi K, Kanogawa N, Kiyono S, Nakamura M, Kondo T, Saito T, Nakagawa R, Ogasawara S, Suzuki E, Nakamoto S, Muroyama R, Kanda T, Maruyama H, Mimura N, Kato J, Motohashi S, Kato N. Effect of Atezolizumab plus Bevacizumab in Patients with Hepatocellular Carcinoma Harboring CTNNB1 Mutation in Early Clinical Experience. J Cancer 2022; 13(8):2656-2661. doi:10.7150/jca.71494. Available from https://www.jcancer.org/v13p2656.htm

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Abstract

Graphic abstract

Atezolizumab plus bevacizumab (ATZ/BV) treatment is a combined immunotherapy consisting of immune checkpoint inhibitor (ICI) and anti-vascular endothelial growth factor monoclonal antibody, which has brought a major paradigm shift in the treatment of unresectable hepatocellular carcinoma (HCC). Gain-of-function mutation of CTNNB1 contributes to resistance of ICI monotherapy through the framework of non-T-cell-inflamed tumor microenvironment. However, whether CTNNB1 mutation renders resistance to ATZ/BV similar to ICI monotherapy remains to be elucidated. In this study, a liquid biopsy sample in plasma of 33 patients with HCC treated with ATZ/BV was subjected to droplet digital PCR for detecting hotspot mutations at the exon 3 of CTNNB1 locus. A total of eight patients (24.2%) exhibited at least one CTNNB1 mutation. The objective response rate (ORR) in patients with wild-type (WT) and mutant (MT) CTNNB1 was 8.0% and 12.5%, respectively, and the disease control rate (DCR) was 68.0% and 87.5%, respectively. No significant difference in both ORR and DCR has been observed between the two groups. The median progression-free survival in patients with WT and MT CTNNB1 was 6.6 and 7.6 months, respectively (not statistically significant). Similarly, no significant difference in overall survival has been observed between patients with WT and MT CTNNB1 (13.6 vs. 12.3 months). In conclusion, the treatment effect of ATZ/BV in patients with HCC with MT CTNNB1 was comparable to those patients with WT CTNNB1. These results implicate that BV added to ATZ might improve immunosuppressive tumor microenvironment caused by CTNNB1 mutation.

Keywords: Liquid biopsy, CTNNB1, atezolizumab plus bevacizumab, HCC